脂肪干细胞在体外特定培养液中向软骨细胞表型的分化

目的:应用转化生长因子β1,体外诱导脂肪干细胞向成软骨细胞表型分化,探讨其作为组织工程化软骨种子细胞的可行性。方法:实验于2005-04/2006-06在华中科技大学同济医学院公卫实验室完成。①取大鼠腹股沟处脂肪,酶消化法分离、培养脂肪干细胞,体外传代培养。②取第3代细胞通过转化生长因子β1、地塞米松和维生素C诱导脂肪干细胞向软骨细胞分化。③诱导后14d观察细胞形态变化,进行阿辛蓝染色检测软骨基质的分泌、免疫组织化学检测细胞Ⅱ型胶原的表达,采用Western-blot和反转录-聚合酶链反应检测诱导前后成软骨相关的Sox9,蛋白聚糖与Ⅱ型胶原的表达。结果:①细胞接种的最初几日,细胞呈圆形,1周后贴壁细胞呈长梭形,体积增大;14d后贴壁生长细胞基本长满单层,中心细胞排列紧密,形态与骨髓间充质干细胞相似。诱导培养后,细胞形态逐渐由梭型向多角形、多边形转变。诱导14d后多数细胞呈平坦的多边角形状细胞;其夹杂多角突起状或多角纺锤状细胞。②诱导后阿辛蓝染色示糖胺聚糖均匀分布于基质中。③免疫组织化学染色示基质中Ⅱ型胶原表达阳性。④反转录-聚合酶链反应检测成软骨相关的Sox9、蛋白聚糖、Ⅱ型胶原mRNA表达阳性。⑤Western-blot印迹检测细胞诱导后Ⅱ型胶原蛋白表达阳性。结论:脂肪干细胞在特定培养液的诱导下可向成软骨细胞表型分化,并能分泌软骨细胞特异性基质,有望成为软骨组织工程新的细胞来源。     

常咯啉在实验性心律失常狗的药代动力学-药效动力学分析

用Harris冠脉结扎法诱发的心律失常狗研究常咯啉药代动力学-药效动力学。7只狗按83.33μg·kg^-1·min^-1静脉滴注60min,在给药期间和停药后不同时间记录ECG及测定血药浓度。C-T数据用药代程序计算药代参数;药效数据用药代-药效同步分析模型计算药效动力学参数,K₁₀, T_1/2,Vd,Cl分别为0.0087min^-1,78.03min,40.55ml·kg^-1和0.421ml·kg^-1·min^-1;K_eO和Ce(50)分别为0.0048min^-1和2.01μg·ml^-1.     

Antihypertensive efficacy and safety of benidipine and its effects on cardiac structure and function in elderly Chinese patients with mild to moderate hypertension: an open-label, long-term study

Benidipine (CAS 91599-74-5) has been reported as an effective antihypertensive treatment and its cardioprotective effects have been shown in several basic and clinical studies. However, the long-term efficacy and safety of benidipine remain unknown in elderly Chinese patient with hypertension. In this prospective, multicenter, open-label clinical trial, 152 eligible patients aged 60 to 75 years with mild to moderate essential hypertension (sitting systolic blood pressure (BP) > or = 140 mmHg and/or sitting diastolic BP > or = 90 mmHg) entered a 52-week study. All patients initially received benidipine 2-4 mg once a day, followed by titration to benidipine 8 mg/day to achieve the target BP (< 140/90 mmHg in non-diabetics and <130/80 mmHg in diabetics). Add-on hydrochlorothiazide (CAS 58-93-5) and/or metoprolol tartaric acid (CAS 3750-58-6) were permitted during the study. Overall, 132 patients completed the 52-week treatment with benidipine as monotherapy or combination therapy. It showed that the regimen based on benidipine provided an obvious mean trough BP reduction of 13.8 +/- 12.4/8.3 +/- 9.2 mmHg (p < 0.001), and 62.5% of patients reached the target BP. In patients with left ventricular hypertrophy, the left ventricular mass index significantly decreased from 147.1 +/- 27.6 g/m2 at baseline to 136.0 +/- 17.5 g/m2 at 52 weeks (p = 0.036). Clinical adverse events (AEs) were found in 15.1% of all patients, and six patients discontinued the treatment due to drug-related AEs during the entire trial. Patients' compliance was an average of 98.7%. Benidipine, with a favorable tolerability profile, provides a long-term antihypertensive effect and potential benefit for the heart in elderly patients with mild to moderate hypertensive, suggesting that it is suitable for elderly patients with hypertension.     

In-111-labeled white blood cell uptake in noninfected closed fracture in humans: prospective study

Since indium-111 white blood cell (In-111 WBC) scintigraphy is often used to evaluate for osteomyelitis in bone fractures, it is important to know if noninfected fractures have In-111 WBC uptake. Twenty-seven noninfected closed fracture sites in 19 patients were prospectively evaluated with technetium-99m methylene diphosphonate bone scintigraphy and In-111 WBC scintigraphy. In-111 WBC uptake was present in 41% of the 27 sites. In the 11 positive sites, the In-111 WBC uptake was 1+ (definite but minimal) in 55%, 2+ (moderate) in 36%, and 3+ (marked) in 9%. The visual intensity of the radioactive uptake on In-111 WBC scintigrams relative to that on bone scintigrams was less in 82%, equal in 9%, and greater in 9%. The visual size of the area of uptake on In-111 WBC scintigrams and bone scintigrams was smaller in 36%, equal in 55%, and greater in 9%. Factors that may help distinction of In-111 WBC uptake due to fracture alone from infection associated with fracture are discussed.     

Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment

Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible.     

美托洛尔治疗右室流出道室性早搏的效果观察

目的：观察美托洛尔对起源于右室流出道室性早搏的疗效。方法：选择起源于右室流出道的室性早搏患25例，给予美托洛尔治疗，剂量从6．25mg开始，无不良反应后，逐渐加量，最大剂量每天100－150mg，疗程3个月，用药前后查12导联体表心电图、24小时动态心电图及结合临床症状进行评定。结果：①临床症状评定：胸闷心悸25例，治疗后减轻20例，有效率为80％；焦虑20例，治疗后症状均消失，有效率为100％；头晕14例，治疗后减轻12例，有效率为85．7％。②室性早搏评定：25例中达到室性早搏抑制率70％有11例，有效率为44％；平均室性早搏抑制率为45．6％，6例成对室性早搏抑制率为80％，3例短阵室速消失，平均心率降低12．6／min。③生化指标：血糖、胆固醇、甘油、三酯治疗前后无明显改变。④2例因血压低未加药量。结论：美托洛尔治疗起源于右室流出道室性早搏疗效肯定，尤其对运动后早搏增多疗效较好，临床太改善较显，观察中未发现明显不良反应，无致心律失常现象。     

Body Surface Mapping and Nontraditional ECG Leads in Patients with Wolff-Parkinson-White Syndrome

A method of ECG mapping from 90 points on the chest surface is described in 41 male and 17 female patients, aged 6 to 59 years. All also underwent invasive electrophysiological investigation and intraoperative epicardial mapping. Fifty-two patients had one, three patients two, and one patient had three anomalous accessory pathways. Two patients had nodoventricular tracts (Mahaim fibers). We distinguished seven zones along the atrioventricular groove (AVG) to compare the data derived from epicardial, endocardial, and body surface mapping. A microcomputer was used for the analysis of all ECGs to construct and analyze the isopotential maps. The criterion for localization of the anomalous accessory pathways was determined after analysis of the data from all 58 patients. The localization criterion was the appearance of a minimal deflection (-0.09 +/- 0.03 mV) on the surface isopotential maps within the first 0.28 msec of the QRS complex. This criterion for localization of anomalous accessory pathways from the chest surface was proposed on the basis of comparison of data from selective coronary angiography, the ventriculogram, and the chest X ray i.e., radiographic-topographic-anatomical data. In 20 patients, 10-20 nontraditional ECG leads were recorded from the chest to reflect the atrioventricular groove. The number of nontraditional ECG leads depended on patient age, weight, and height. Localization of the accessory pathway in one of the seven zones was established by the earliest delta wave and its maximum deviation. It was possible to localize the anomalous accessory pathway and to suspect multiple pathways in 95% of cases using nontraditional ECG leads and the listed criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L- arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.